Metabolic Deregulation in Pulmonary Hypertension

Authors

Rajamma Mathew, Department of Pediatrics, New York Medical College, Valhalla, NY 10595, USA.Follow
Sanda Iacobas, Department of Pathology, New York Medical College, Valhalla, NY 10595, USA.Follow
Jing Huang, Department of Pathology and Laboratory Medicine, Rutgers University Biomedical and Health Sciences, New Brunswick, NJ 08901, USA.
Dumitru Andrei Iacobas, Personalized Genomics Laboratory, Texas Undergraduate Medical Academy, Prairie View A&M University, Prairie View, TX 77446, USA.

Author Type(s)

Faculty

DOI

10.3390/cimb45060309

Journal Title

Current Issues in Molecular Biology

First Page

4850

Last Page

4874

Document Type

Article

Publication Date

6-3-2023

Department

Pediatrics

Keywords

Cav1, Nfe2l2, Ngf, PAH channelopathy, Pmm2, Slc2a1, citrate cycle, fructose and mannose pathway, glycolysis/gluconeogenesis pathway, pyruvate metabolism

Disciplines

Medicine and Health Sciences

Abstract

The high morbidity and mortality rate of pulmonary arterial hypertension (PAH) is partially explained by metabolic deregulation. The present study complements our previous publication in "Genes" by identifying significant increases of the glucose transporter solute carrier family 2 (Slc2a1), beta nerve growth factor (Ngf), and nuclear factor erythroid-derived 2-like 2 (Nfe2l2) in three standard PAH rat models. PAH was induced by subjecting the animals to hypoxia (HO), or by injecting with monocrotaline in either normal (CM) or hypoxic (HM) atmospheric conditions. The Western blot and double immunofluorescent experiments were complemented with novel analyses of previously published transcriptomic datasets of the animal lungs from the perspective of the Genomic Fabric Paradigm. We found substantial remodeling of the citrate cycle, pyruvate metabolism, glycolysis/gluconeogenesis, and fructose and mannose pathways. According to the transcriptomic distance, glycolysis/gluconeogenesis was the most affected functional pathway in all three PAH models. PAH decoupled the coordinated expression of many metabolic genes, and replaced phosphomannomutase 2 (Pmm2) with phosphomannomutase 1 (Pmm1) in the center of the fructose and mannose metabolism. We also found significant regulation of key genes involved in PAH channelopathies. In conclusion, our data show that metabolic dysregulation is a major PAH pathogenic factor.

Recommended Citation

Mathew, R., Iacobas, S., Huang, J., & Iacobas, D. A. (2023). Metabolic Deregulation in Pulmonary Hypertension. Current Issues in Molecular Biology, 45 (6), 4850-4874. https://doi.org/10.3390/cimb45060309